Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Hinks, Anne; Eyre, Steve; Ke, Xiayi; Barton, Anne; Martin, Paul; Flynn, Edward; Packham, Jon; Worthington, Jane; Thomson, Wendy

doi:10.1038/gene.2009.105

Cited by 56 publications

(48 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The odds ratios for the minor allele ranged from 0.34 for rs13151961 to 0.46 for rs6840978. The demonstrated odds ratios of <1.0 suggest protective effects of the minor alleles on PSC susceptibility similar to the association observed for other immune-mediated diseases [8,9,10,11,12,14,16,17,20]. In line with that, homozygosity for the major allele was positively associated with development of PSC when examining rs13151961 (p = 0.014, OR 3.03, 95% CI 1.18–7.76), rs13119723 (p = 0.036, OR 2.53, 95% CI 1.06–6.06) or rs6822844 (p = 0.037, OR 2.45, 95% CI 1.02–5.86).…”

Section: Resultsmentioning

confidence: 85%

“…The association of the IL2/IL21 region on chromosome 4q27 with celiac disease [12], type 1 diabetes [13,14,15], rheumatoid arthritis [14,16,17], psoriatic arthritis [18], juvenile idiopathic arthritis [19,20], systemic lupus erythematosus [17,21], Sjögren’s syndrome [17] and Grave’s disease [15] suggests this region as a general autoimmune risk locus and makes it also an interesting candidate locus for PBC. The frequency of classic autoimmune diseases is increased in both PSC patients and PBC patients and their first-degree relatives [22,23].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Stallhofer¹,

Denk²,

Glas

et al. 2011

Digestion

View full text Add to dashboard Cite

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC.

show abstract

Section: Resultsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Stallhofer¹,

Denk²,

Glas

et al. 2011

Digestion

View full text Add to dashboard Cite

show abstract

“…The locus has been associated with RA susceptibility in Europeans (4,10) as well as SLE and juvenile idiopathic arthritis (10,55,56). rs9653442 in particular has been the subject of several investigations as an autoimmune risk variant, and it was the index variant for RA risk in a trans-ethnic meta-analysis (10).…”

Section: Discussionmentioning

confidence: 99%

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans

Danila

Laufer

Reynolds

et al. 2017

Mol Med

View full text Add to dashboard Cite

More than 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibodypositive RA and 933 African American controls on the Immunochip (iChip) array. Using multivariable regression, we evaluated the association between iChip markers and the risk of RA and radiographic severity. The single nucleotide polymorphism (SNP) rs1964995 (odds ratio = 1.97, p = 1.28 × 10 -15 ) near HLA-DRB1 was the most strongly associated risk SNP for RA susceptibility; SNPs in AFF3, TNFSF11 and TNFSF18 loci were suggestively associated (10 -4 < p < 3.1 × 10 -6). Trans-ethnic fine mapping of AFF3 identified a 90% credible set containing previously studied variants, including rs9653442, rs7608424 and rs6712515, as well as the novel candidate variant rs11681966; several of these likely influence AFF3 gene expression level. Variants in TNFRSF9, CTLA4, IL2RA, C5/TRAF1 and ETS1 -but no variants within the major histocompatibility complex -were associated with RA radiographic severity. Conditional regression and pairwise linkage disequilibrium (LD) analyses suggest that additional pathogenic variants may be found in ETS1 and IL2RA beyond those found in other ethnicities. In summary, we used the dense genotyping of the iChip array and the unique LD structure of African Americans to validate known risk loci for RA susceptibility and radiographic severity, and to better characterize the associations of AFF3, ETS1 and IL2RA.

show abstract

“…AFF3 has been found a susceptibility gene in autoimmune diseases, namely rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis (Barton et al, 2009;Castelino and Barton, 2010;Hinks et al, 2010). AFF3 is deleted in Nievergelt syndrome, an autosomal dominant mesomelic dysplasia (Steichen-Gersdorf et al, 2008).…”

Section: Aff3mentioning

confidence: 99%

t(2;21)(q11;q22)

Huret¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

View full text Add to dashboard Cite

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Cited by 56 publications

References 33 publications

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans

t(2;21)(q11;q22)

Contact Info

Product

Resources

About